Cleansing composition



United States Patent 3,355,387 CLEANSING COMPOSITION Emil T. Hinkel, .lr., Bethlehem, N.Y., assignor to Sterling Drug !nc., New York, N.Y., a corporation of Delaware No Drawing. Filed Dec. 8, 1965, Ser. No. 512,520 3 Claims. (Cl. 252-106) This application is a continuation-in-part of the copending Hinkel Jr. application, Serial No. 331,908 filed December 19, 1963, and now abandoned.

This invention relates to an antibacterial sudsing detergent. More particularly the invention is concerned with an improvement in non-soap cleansing compositions of the type described in United States Patent 2,303,932.

The compositions described in the above-mentioned patent have met with outstanding success for over a decade as fast-acting, thorough, personal cleansing agents in hospitals and homes. More recently, such compositions with added hexachlorophene or bis(2-hydroxy-3,5,6-trichlorophenyl)rnethane have been of special value to operating room teams, surgical patients, hospital personnel and others coming in contact with pathogenic bacteria. These compositions are more efiicient and more rapid in action than are the age-old soaps which, because of their inherent alkalinity, are, among other things, irritating to the skin and inefiective in acid media.

Compositions with hexachlorophene made according to the teaching of the above patent have the same pH as normal skin and hence, rather than removing the normal acid mantle of the skin as does soap, actually deposit an emollient antiseptic film which can be built up and maintained by continued use. The compositions can therefore be used as brushless scrubs in preparing both the skin of a patient as well as the surgeons hand for operation. Repeated and extensive studies have shown these preparations to be as efficacious in eliminating skin bacteria as preparations requiring three times as much time while greatly lowering the incidence of skin irritation.

The above-mentioned compositions do, however, have certain inherent deficiencies which, in particular instances, rule out their use.

Certain gram-negative organisms, particularly of the coliform and pseudomonas groups, are common contaminants of the skin and other surface areas susceptible to the application of antibacterially active detergent compositions. It is therefore important to reduce or eliminate these organisms along with the gram-positive organisms such as cocci to attain and maintain minimal bacterial contamination. However, antibacterial agents which have been used in combination with detergents of various types, while having in certain instances some effect on gramnegative organisms, require either an irritatingly high concentration or too long an exposure time. For example, the following representative antibacterial agents when added to hexachlorophene-containing compositions prepared as described in the above-mentioned patent gave preparations which were either ineffective or effective only at high concentrations against gram-negative organisms such as E. coli and Ps. aeruginom: benzoic acid and its derivatives such as salicyclic, 4-methylbenzoic, 4- chlorobenzoic and 3,4-dichlorobenzoic acids; benzyl alcohol and its derivatives such as 3,4-dichlorobenzyl and 2,4-dichlorobenzyl alcohols; phenols such as o-phenylphenol, 4-chloro-2-propylphenol, 4-chloro-2-hexylphenol,

4-chloro 3,S-dimethylphenol and bis(2-hydroxy-5-chloro- 'phenyl)methane; and halosalicylanilides such as 3,4,4- trichlorocarbanilide, 3,5,3',4-tetrachlorosalicylanilide and 5-chloro-4-nitrosalicylanilide.

In accordance with the present invention, there are provided stable, sudsing, non-soap cleansing preparations which exhibit a high level of antibacterial activity against gram-negative organisms while retaining gram-positive antibacterial activity. The new compositions consist of aqueous emulsions of the type described in U.S. Patent 2,303,932 optionally but preferably containing hexachlorophene and, according to the present invention, also containing a halogenated salicylic acid of the general formula wherein X is a halogen and therefore including fluorine, chlorine, bromine and iodine and n is a number from 1 to 3. The compounds are members of a known class and generally are prepared by the nuclear halogenation of salicylic acid or by replacement by halogen of the diazotized amino group of an aminosalicylic acid.

The preferred compounds in the general class are the monohalogenated salicylic acids exemplified by S-bromosalicylic acid, 3-fluorosalicylic acid, 6-chlorosalicylic acid and 4-iodosalicylic acid with the S-bromosalicylic acid being especially preferred. The dihalogenated salicylic acids exemplified by 3,5-difiuorosalicylic acid, 3,5-dichlorosalicylic acid, 3,5-dibromosalicylic acid and 3,5- diiodosalicylic acid, While exhibiting slightly higher antibacterial activity, are less desirable in certain instances because of ther slow in vivo metabolism. The amount of the halogenated salicylic acid can be varied somewhat but ordinarily it is preferred to employ 0.11.0% by Weight.

The emulsion to which the halogenated salicylic .acid is added includes an anionic detergent of the alkylphenoxypolyalkylene ether sulfonate type, petrolatum, lanolin, or other conventional oleaginous base materials, thickening agents, preservatives, etc.

The alkylphenoxypolyalkylene ether sulfonate emulsi-- fying agents useful in practising the invention are the surface active agents described in U.S. Patent 2,115,192, issued April 26, 1938 which are prepared by condensing an alkylphenol with a dihalopolyalkylene ether and reacting the product obtained with a metal sulphite. Particularly useful alkylphenoxypolyalkylene ether sulfonates for the purposes of this invention are the p-tertiary octylphenoxypolyalkylene ether sulfonates produced by condensing ptertiary octylphenoxypolyalkylene ether halides with a metal sulfite. A preferred compound of this group is the product containing three ether groups per p-tertiary octylpheny-l nucleus, an approximately 28% aqueous dispersion of which is known under the name Triton X-200 and also under the designation Entsufon.

The alkylphenoxypolyalkylene ether sulfonate is used in amounts from 10% to about 20% by weight in the compositions. Ordinarily, for general use it is preferable to use about 14% by weight of the sulfonate although in particular circumstances higher or lower percentages may be more useful.

The remaining major constituent of the emulsion is, of course, water which generally is present in amounts ranging from 60% to 80% by weight along with preservatives, smoothing agents, emulsifiers, chelating agents and other conventional pharmaceutical excipients.

The emulsion when ready for use is at a pH of -6, preferably pH 5.5, the pH of the skin, as attained by conventional addition of acid, e.g. hydrochloric, or base, e.g. sodium hydroxide, as required.

The germicidal efiiciency of the compositions of the invention against certain organisms particularly S. aureus, Ps. aeruginosa and E. coli, was determined by a modification of the survival on exposure test described by Weber and Black, Am. J. Pub. Health 3 8, 1405 (1948). In this procedure the compositions were diluted 1:5 w/w with sterile water and ml. aliquots of the diluted formulation were inoculated with 0.1 m1. of buffer suspension of an appropriate agar slant culture at room temperature. At predetermined time intervals a one milliliter portion of the inoculated formulation was removed and plated on a tryptone glucose extract lecithin agar and incubated for 48 hours at 37 C. The number of organisms on each plate was then determined in the usual way.

The following examples will further illustrate the invention without the latter being limited thereto.

Example 1 A sudsing detergent was made up according to the following formula:

Water, deionized, q.s. ad 100.00

1 Sullicient acid to adjust to pH 5.5.

Example 2 The composition of Example 1 was modified by the addition of 0.03 mole (0.67% by weight) of 5-bromosalicylic acid.

Example 3 The composition of Example 1 was modified by the addition of 0.01 mole (0.22% by weight) of 5-bromosalicylic acid.

Example 4 The composition of Example 1 was modified by the addition of 0.031 mole (0.67% by weight) of 3,5-di bromosalicylic acid.

Example 5 The composition of Example 1 was modified by the addition of 0.01 mole (0.3% by weight) of 3,5-dibromosalicylic acid.

Example 6 The composition of Example 4 was modified by the omission of hexachlorophene, i.e. the composition of Example l modified by addition of 0.031 mole of 3,5-dibromosalicylic acid and omission of the 3% hexachlorophene.

The following comparative tests illustrate the increased gram-negative antibacterial activity of the compositions of the present invention. Tables I and II show the results 4 obtained using the compositions of Examples 2 and 3 and 4 and 5 respectively on the gram-negative organisms E. coli and Ps. aeruginosa compared with the composition of Example 1.

TABLE I Number of survivors/ml, following exposure to- Number of survivors/m1. following exposure to Time following E. coli (74Xl0/rnl.) Ps. aeruginosa (103Xl0/m1.) exposure i (111111.) l

E11 Ex4iEx5 Ex.1 Ex.4 Ex.5

l i 1,990 trio tnc 10 8,500 10 9,800 tne 10 160 10 10 tne 10 110 10 10 tnc 10 90 Too numerous to count.

It is evident that the compositions of Examples 2, 3, 4 and 5 illustrating several levels of added halogenated salicylic acids markedly increase the antibacterial effect on gram-negative organisms. The marked reduction in the number of gram-negative organisms is attributed to the presence of the halogenated salicylic acid and not to a possible synergistic action with hexachlorophene. This is illustrated by comparison of the compositions of Examples l and 6 in Table 111.

TABLE III Number of survivors/ml. following exposure to Time followlng(ex pos)ure E. coli (90 l0/ml.) Pa. aeruainosa (103X10 /ml.)

Ex. 1 Ex. 6 Ex. 1 Ex. 6

tnc 0 0 0 0 0 0 0 0 0 0 Too numerous to count.

In each of the following examples the composition of Example 1 was modified by the addition of the indicated acids:

The germicidal efiectiveness of compositions incorporatmg the class of other halogenated salicylic acids (Examples 944) of the invention as compared to the compositions of Examples 1, 7 and 8 is illustrated in Table IV (0.01 molar in indicated acid) and Table V (0.03 molar in indicated acid).

TABLE IV Time N o. of survivors/ml. followlng exposure to following exposure E. coli (74X10/m1.) Pa. aeruginosa (103Xl0/ml.)

(min.)

Ex. 1 Ex. 7 Ex. 9 Ex. 11 Ex. 13 Ex. 1 Ex. 7 EX. 9 Ex. 11 Ex. 13

[7110* tn:- tnc fmtno tnc tnc im- 27, 300 3, 700 8,500 1,930 tnc tnc tnc 70 1,060 680 mo snc tnc 740 70 10 tne tnc 20, 300 10 620 *Too numerous to count.

TABLE V No. of survivors/ml. followlng exposure to-- Time following exposure E. coli (74 lO/ml.) Pa. ueruainasa (103X10 /m1.)

(min.)

Ex. 1 Ex. 8 Ex. 10 Ex. 12 Ex. 14 Ex. 1 Ex. 8 Ex. 10 I Ex. 12 I Ex. 14

in! tnr' tnc tnc 240 10 tnc 31, 000 6, 400 35, 400 10 10 *Too numerous to count.

I claim: References Cited iii i ff fii fi1ff UNITED STATES PATENTS seniayo an aqueu em S B. y alkylene ether sulfonate containing 0.11.0% by Weight of 22 et a1 1 1 a halogenated salicylic acid of the folmu a 2,115,192 4/1938 Bruson 252 353 COOH 40 2,303,932 12/1942 Guild 252 142 (Xh 2,599,140 6/1952 Taub 252l07 3,072,525 1/1963 Neumann 252l07 h X h I d h f 1 t 3 th OTHER REFERENCES W erein 1S 8 ogen an n 18 a Ill-1H1 81 mm 0 6 amount of said sulfonate being between 10 and 20% of Rochalx et al.. Bactericidal action of certain halogen said composition by weight, said emulsion having a pH of 5-6.

2. A stable, non-soap cleansing composition in accordance with claim 1 in which the alkylphenoxypolyalkylene ether sulfonate is p-tertiary octylphenoxyethoxyethyl ether sulfonate.

derivatives of salicylic acid, Chem. Abstracts, vol. 22, p. 443.

LEON D. ROSDOL, Primary Examiner. W. E. SCHULZ, Assistant Examiner. 

1. A STABLE, NON-SOAP CLEANSING COMPOSITION CONSISTING ESSENTIALLY OF AN AQUEOUS EMUSION OF ALKYLPHENOXYLPOLYALKYLENE ETHER SULFONATE CONTAINING 0.1-1.0% BY WEIGHT OF A HALOGENATED SALICYLIC ACID OF THE FORMULA 